Replacement surfactant therapy containing phospholipids and 1% weight hydrophobic surfactant proteins (SP-B and SP-C) from animal source has been proven clinically to stabilize patients with respiratory distress syndrome (RDS) due to its ability to spread rapidly and lower surface tension to near zero values at rates required to prevent lung collapse. A new generation of synthetic lung surfactant is being developed based on peptide analogs and peptoids of SP-B and SP-C to address the cost of the treatment. For the effective design of this new synthetic surfactant a detailed study must be carried-out, to address, three essential properties whose mechanism is not well understood for these surfactants. First, the squeeze-out of unsaturated or unordered structures to prevent lung collapse. Secondly, reuptake essential for stabilizing the lung after expiration (squeeze-out). Thirdly, is the role of the hydrophobic protein SP-C during squeeze-out and re-uptake. These experiments would naturally be followed by the evaluation of several synthetic peptides and peptoid mimics proposed for the design of the synthetic surfactant. The synthetic peptides and peptoids must have similar properties to that of SP-C found to be essential in natural exogenous surfactant preparations. We propose that SP-C enhances the rate of squeeze-out of unsaturated or unordered components to prevent lung collapse, For this, we will study model binary and ternary mixtures of phospholipid and SP-C, peptide analogs, and peptoids using IRRAS, ATR-FT-IR, PM-IRRAS, AFM, epifluorescence spectroscopies, bubble surfactometry and computational simulations, Our aims are: (1) To simulate the squeeze-out and re-uptake process for binary and ternary mixtures of phospholipids. (2) To study via IRRAS the effect of SP-C on the squeeze-out and re-uptake of phopholipids. (3) To study via computational techniques the effect of SP-C on the squeeze-out and re-uptake of phospholipids. (4) To compare the secondary structure of SP-C with the peptide analogs using FT-IR spectroscopy. (5) To study the lipid-peptide interactions using ATR-FT-IR and transmission FT-IR spectroscopy. (6) To study the lipid peptide interactions at the ANV interface by IRRAS and determine if these peptides and peptoids enhance squeeze-out and re-uptake. (7) To study the surfactant film properties by several biophysical techniques. (8)To simulate the peptides at an A/W interface using the experimental results obtained. This interdisciplinary approach towards the study of this vital substance will provide a molecular level understanding of the dynamics that occur at or near the A/W interface and explore several synthetic peptides that may be used for the design of a new exogenous surfactant.